协和医学杂志2026，Vol.17Issue(1)：23-32,10.DOI:10.12290/xhyxzz.2025-0996
阿霉素与脓毒症所致心肌损伤的机制:差异性与趋同性
Mechanism Exploration of Doxorubicin and Sepsis Induced Myocardial Injury:Differences and Convergences
摘要
Abstract
Doxorubicin(DOX)-induced cardiotoxicity and sepsis-induced myocardial injury(SIMI)represent significant clinical challenges in patients undergoing chemotherapy,sharing a common pathological basis of oxidative stress and mitochondrial dysfunction.Ferroptosis,an iron-dependent form of regulated cell death driven by lipid peroxidation,has recently been shown to play a critical role in DOX-induced cardiotoxicity and lipopolysaccharide(LPS)-induced SIMI.This article systematically reviews the mechanisms underlying myocardial injury caused by DOX and sepsis,identifying ferroptosis as a central common pathway.DOX triggers a burst of reactive oxygen species within mitochondria and inhibits glutathione peroxidase 4(GPX4)activity through redox cycling of its quinone group and high-affinity accumulation in mitochondrial cardiolipin.LPS,by activating pattern recognition receptors and related inflammatory signaling pathways,provokes a cytokine storm and mitochondrial dysfunction.Both can disrupt the core regulatory axis of cysteine-glutathione(GSH)-GPX4,synergistically promoting ferroptosis in cardiomyocytes.Moreover,epigenetic regulation plays a key role in DOX-and LPS-induced cardiomyocyte ferroptosis and may serve as a promising therapeutic target.A deeper un-derstanding of the ferroptosis mechanism and its epigenetic regulatory network in the synergistic injury induced by DOX and sepsis is of great importance for developing novel strategies to mitigate chemotherapy-related car-diotoxicity and improve outcomes in cancer patients with concurrent infections.关键词
阿霉素/脓毒症/心肌损伤/铁死亡/氧化应激/表观遗传Key words
doxorubicin/sepsis/myocardial injury/ferroptosis/oxidative stress/epigenetics分类
医药卫生引用本文复制引用
张涛,南子涵,刘丽霞,刘佳琪,陈秀凯,王小亭,苏素文..阿霉素与脓毒症所致心肌损伤的机制:差异性与趋同性[J].协和医学杂志,2026,17(1):23-32,10.基金项目
国家科技部重大专项-四大慢病(2024ZD0526105) National Key Research and Development Program of China-Major Project on Four Major Chronic Noncommunicable Diseases(2024ZD0526105) （2024ZD0526105）
